The enzyme was discovered by Leonard T. Skeggs Jr. in 1956.[6] The first crystaw structure of human testis ACE was sowved in de year 2002 by R. Natesh in de wab of K. Ravi Acharya and de work was pubwished in de journaw Nature in de January 2003. [7] It is wocated mainwy in de capiwwaries of de wungs but can awso be found in endodewiaw and kidney epidewiaw cewws.[8]

Anatomicaw diagram of de renin–angiotensin system, showing de rowe of ACE at de wungs.[11]

ACE hydrowyzes peptides by de removaw of a dipeptide from de C-terminus. Likewise it converts de inactive decapeptide angiotensin I to de octapeptide angiotensin II by removing de dipeptide His-Leu.[12]

ACE is a zinc metawwoproteinase.[15] The zinc ion is essentiaw to its activity, since it directwy participates in de catawysis of de peptide hydrowysis. Therefore, ACE can be inhibited by metaw-chewating agents.[16]

The E384 residue was found to have a duaw function, uh-hah-hah-hah. First it acts as a generaw base to activate water as a nucweophiwe. Then it acts as a generaw acid to cweave de C-N bond.[17]

The function of de chworide ion is very compwex and is highwy debated. The anion activation by chworide is a characteristic feature of ACE.[18] It was experimentawwy determined dat de activation of hydrowysis by chworide is highwy dependent on de substrate. Whiwe it increases hydrowysis rates for e.g. Hip-His-Leu it inhibits hydrowysis of oder substrates wike Hip-Awa-Pro.[17] Under physiowogicaw conditions de enzyme reaches about 60% of its maximaw activity toward angiotensin I whiwe it reaches its fuww activity toward bradykinin, uh-hah-hah-hah. It is derefore assumed dat de function of de anion activation in ACE provides high substrate specificity.[18] Oder deories say dat de chworide might simpwy stabiwize de overaww structure of de enzyme.[17]

The ACE gene, ACE, encodes two isozymes. The somatic isozyme is expressed in many tissues, mainwy in de wung, incwuding vascuwar endodewiaw cewws, epidewiaw kidney cewws, and testicuwarLeydig cewws, whereas de germinaw is expressed onwy in sperm. Brain tissue has ACE enzyme, which takes part in wocaw RAS and converts Aβ42 (which aggregates into pwaqwes) to Aβ40 (which is dought to be wess toxic) forms of beta amywoid. The watter is predominantwy a function of N domain portion on de ACE enzyme. ACE inhibitors dat cross de bwood–brain barrier and have preferentiawwy sewected N-terminaw activity may derefore cause accumuwation of Aβ42 and progression of dementia.[citation needed]

ACE in compwex wif inhibitor wisinopriw, zinc cation shown in grey, chworide anions in yewwow. Based on PyMOL rendering of PDB 1o86 The picture shows dat wisinopriw is a competitive inhibitor, since it has a simiwar structure to angiotensin I and binds to de active site of ACE. The structure of ACE and wisinopriw compwex was sowved in de year 2002 and pubwished in 2003. [7]

ACE inhibitors inhibit ACE competitivewy.[19] That resuwts in de decreased formation of angiotensin II and decreased metabowism of bradykinin, which weads to systematic diwation of de arteries and veins and a decrease in arteriaw bwood pressure. In addition, inhibiting angiotensin II formation diminishes angiotensin II-mediated awdosterone secretion from de adrenaw cortex, weading to a decrease in water and sodium reabsorption and a reduction in extracewwuwar vowume.[20]

ACE's effect on Awzheimer's disease is stiww highwy debated. Awzheimer patients usuawwy show higher ACE wevews in deir brain, uh-hah-hah-hah. Some studies suggest dat ACE inhibitors dat are abwe to pass de bwood-brain-barrier (BBB) couwd enhance de activity of major amywoid-beta peptide degrading enzymes wike nepriwysin in de brain resuwting in a swower devewopment of Awzheimer's disease.[21] More recent research suggests dat ACE inhibitors can reduce risk of Awzheimer's disease in de absence of apowipoprotein E4 awwewes (ApoE4), but wiww have no effect in ApoE4- carriers.[22] Anoder more recent hypodesis is dat higher wevews of ACE can prevent Awzheimer's. It is assumed dat ACE can degrade beta-amywoid in brain bwood vessews and derefore hewp prevent de progression of de disease.[23]

A negative correwation between de ACE1 D-awwewe freqwency and de prevawence and mortawity of COVID-19 has been estabwished.[24]

The I awwewe is found wif increased freqwency in ewite distance runners, rowers and cycwists. Short distance swimmers show an increased freqwency of de D-awwewe, since deir discipwine rewies more on strengf dan endurance.[27][28]